CFR 2013 Title21 Vol3

Title 21 Food and Drugs

Parts 170 to 199

Revised as of April 1, 2013

Containing a codification of documents of general applicability and future effect

As of April 1, 2013

Published by the Office of the Federal Register National Archives and Records Administration as a Special Edition of the Federal Register

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U.S. GOVERNMENT OFFICIAL EDITION NOTICE

Legal Status and Use of Seals and Logos

The seal of the National Archives and Records Administration (NARA) authenticates the Code of Federal Regulations (CFR) as the official codification of Federal regulations established under the Federal Register Act. Under the provisions of 44 U.S.C. 1507, the contents of the CFR, a special edition of the Federal Register, shall be judicially noticed. The CFR is prima facie evidence of the origi-nal documents published in the Federal Register (44 U.S.C. 1510).

It is prohibited to use NARAs official seal and the stylized Code of Federal Regulations logo on any republication of this material without the express, written permission of the Archivist of the United States or the Archivists designee. Any person using NARAs official seals and logos in a manner inconsistent with the provisions of 36 CFR part 1200 is subject to the penalties specified in 18 U.S.C. 506, 701, and 1017.

Use of ISBN Prefix

This is the Official U.S. Government edition of this publication and is herein identified to certify its authenticity. Use of the 016 ISBN prefix is for U.S. Government Printing Office Official Edi-tions only. The Superintendent of Documents of the U.S. Govern-ment Printing Office requests that any reprinted edition clearly be labeled as a copy of the authentic work with a new ISBN.

U .S . GOVERNMENT PRINTING OFFICE

U.S. Superintendent of Documents Washington, DC 204020001

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Phone: toll-free (866) 512-1800; DC area (202) 512-1800

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Table of Contents Page

Explanation ................................................................................................ v

Title 21:

Chapter IFood and Drug Administration, Department of Health and Human Services (Continued) ................................................. 3

Finding Aids:

Table of CFR Titles and Chapters ....................................................... 605

Alphabetical List of Agencies Appearing in the CFR ......................... 625

List of CFR Sections Affected ............................................................. 635


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Cite this Code: CFR

To cite the regulations in this volume use title, part and section num-ber. Thus, 21 CFR 170.3 refers to title 21, part 170, section 3.


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Explanation

The Code of Federal Regulations is a codification of the general and permanent rules published in the Federal Register by the Executive departments and agen-cies of the Federal Government. The Code is divided into 50 titles which represent broad areas subject to Federal regulation. Each title is divided into chapters which usually bear the name of the issuing agency. Each chapter is further sub-divided into parts covering specific regulatory areas.

Each volume of the Code is revised at least once each calendar year and issued on a quarterly basis approximately as follows:

Title 1 through Title 16..............................................................as of January 1 Title 17 through Title 27 .................................................................as of April 1 Title 28 through Title 41 ..................................................................as of July 1 Title 42 through Title 50.............................................................as of October 1

The appropriate revision date is printed on the cover of each volume.

LEGAL STATUS

The contents of the Federal Register are required to be judicially noticed (44 U.S.C. 1507). The Code of Federal Regulations is prima facie evidence of the text of the original documents (44 U.S.C. 1510).

HOW TO USE THE CODE OF FEDERAL REGULATIONS

The Code of Federal Regulations is kept up to date by the individual issues of the Federal Register. These two publications must be used together to deter-mine the latest version of any given rule.

To determine whether a Code volume has been amended since its revision date (in this case, April 1, 2013), consult the List of CFR Sections Affected (LSA), which is issued monthly, and the Cumulative List of Parts Affected, which appears in the Reader Aids section of the daily Federal Register. These two lists will identify the Federal Register page number of the latest amendment of any given rule.

EFFECTIVE AND EXPIRATION DATES

Each volume of the Code contains amendments published in the Federal Reg-ister since the last revision of that volume of the Code. Source citations for the regulations are referred to by volume number and page number of the Federal Register and date of publication. Publication dates and effective dates are usu-ally not the same and care must be exercised by the user in determining the actual effective date. In instances where the effective date is beyond the cut- off date for the Code a note has been inserted to reflect the future effective date. In those instances where a regulation published in the Federal Register states a date certain for expiration, an appropriate note will be inserted following the text.

OMB CONTROL NUMBERS

The Paperwork Reduction Act of 1980 (Pub. L. 96511) requires Federal agencies to display an OMB control number with their information collection request.


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Many agencies have begun publishing numerous OMB control numbers as amend-ments to existing regulations in the CFR. These OMB numbers are placed as close as possible to the applicable recordkeeping or reporting requirements.

PAST PROVISIONS OF THE CODE

Provisions of the Code that are no longer in force and effect as of the revision date stated on the cover of each volume are not carried. Code users may find the text of provisions in effect on any given date in the past by using the appro-priate List of CFR Sections Affected (LSA). For the convenience of the reader, a List of CFR Sections Affected is published at the end of each CFR volume. For changes to the Code prior to the LSA listings at the end of the volume, consult previous annual editions of the LSA. For changes to the Code prior to 2001, consult the List of CFR Sections Affected compilations, published for 1949- 1963, 1964-1972, 1973-1985, and 1986-2000.

[RESERVED] TERMINOLOGY

The term [Reserved] is used as a place holder within the Code of Federal Regulations. An agency may add regulatory information at a [Reserved] loca-tion at any time. Occasionally [Reserved] is used editorially to indicate that a portion of the CFR was left vacant and not accidentally dropped due to a print-ing or computer error.

INCORPORATION BY REFERENCE

What is incorporation by reference? Incorporation by reference was established by statute and allows Federal agencies to meet the requirement to publish regu-lations in the Federal Register by referring to materials already published else-where. For an incorporation to be valid, the Director of the Federal Register must approve it. The legal effect of incorporation by reference is that the mate-rial is treated as if it were published in full in the Federal Register (5 U.S.C. 552(a)). This material, like any other properly issued regulation, has the force of law.

What is a proper incorporation by reference? The Director of the Federal Register will approve an incorporation by reference only when the requirements of 1 CFR part 51 are met. Some of the elements on which approval is based are:

(a) The incorporation will substantially reduce the volume of material pub-lished in the Federal Register.

(b) The matter incorporated is in fact available to the extent necessary to afford fairness and uniformity in the administrative process.

(c) The incorporating document is drafted and submitted for publication in accordance with 1 CFR part 51.

What if the material incorporated by reference cannot be found? If you have any problem locating or obtaining a copy of material listed as an approved incorpora-tion by reference, please contact the agency that issued the regulation containing that incorporation. If, after contacting the agency, you find the material is not available, please notify the Director of the Federal Register, National Archives and Records Administration, 8601 Adelphi Road, College Park, MD 20740-6001, or call 202-741-6010.

CFR INDEXES AND TABULAR GUIDES

A subject index to the Code of Federal Regulations is contained in a separate volume, revised annually as of January 1, entitled CFR INDEX AND FINDING AIDS. This volume contains the Parallel Table of Authorities and Rules. A list of CFR titles, chapters, subchapters, and parts and an alphabetical list of agencies pub-lishing in the CFR are also included in this volume.


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An index to the text of Title 3The President is carried within that volume. The Federal Register Index is issued monthly in cumulative form. This index

is based on a consolidation of the Contents entries in the daily Federal Reg-ister.

A List of CFR Sections Affected (LSA) is published monthly, keyed to the revision dates of the 50 CFR titles.

REPUBLICATION OF MATERIAL

There are no restrictions on the republication of material appearing in the Code of Federal Regulations.

INQUIRIES

For a legal interpretation or explanation of any regulation in this volume, contact the issuing agency. The issuing agencys name appears at the top of odd-numbered pages.

For inquiries concerning CFR reference assistance, call 2027416000 or write to the Director, Office of the Federal Register, National Archives and Records Administration, 8601 Adelphi Road, College Park, MD 20740-6001 or e-mail [email protected].

SALES

The Government Printing Office (GPO) processes all sales and distribution of the CFR. For payment by credit card, call toll-free, 866-512-1800, or DC area, 202- 512-1800, M-F 8 a.m. to 4 p.m. e.s.t. or fax your order to 202-512-2104, 24 hours a day. For payment by check, write to: US Government Printing Office New Orders, P.O. Box 979050, St. Louis, MO 63197-9000.

ELECTRONIC SERVICES

The full text of the Code of Federal Regulations, the LSA (List of CFR Sections Affected), The United States Government Manual, the Federal Register, Public Laws, Public Papers of the Presidents of the United States, Compilation of Presi-dential Documents and the Privacy Act Compilation are available in electronic format via www.ofr.gov. For more information, contact the GPO Customer Con-tact Center, U.S. Government Printing Office. Phone 202-512-1800, or 866-512-1800 (toll-free). E-mail, [email protected].

The Office of the Federal Register also offers a free service on the National Archives and Records Administrations (NARA) World Wide Web site for public law numbers, Federal Register finding aids, and related information. Connect to NARAs web site at www.archives.gov/federal-register.

The e-CFR is a regularly updated, unofficial editorial compilation of CFR ma-terial and Federal Register amendments, produced by the Office of the Federal Register and the Government Printing Office. It is available at www.ecfr.gov.

CHARLES A. BARTH, Director, Office of the Federal Register. April 1, 2013.


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THIS TITLE

Title 21FOOD AND DRUGS is composed of nine volumes. The parts in these volumes are arranged in the following order: Parts 199, 100169, 170199, 200299, 300499, 500599, 600799, 8001299 and 1300 to end. The first eight volumes, con-taining parts 11299, comprise Chapter IFood and Drug Administration, Depart-ment of Health and Human Services. The ninth volume, containing part 1300 to end, includes Chapter IIDrug Enforcement Administration, Department of Jus-tice, and Chapter IIIOffice of National Drug Control Policy. The contents of these volumes represent all current regulations codified under this title of the CFR as of April 1, 2013.

For this volume, Susannah C. Hurley was Chief Editor. The Code of Federal Regulations publication program is under the direction of Michael L. White, as-sisted by Ann Worley.


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Title 21Food and Drugs

(This book contains parts 170 to 199)

Part

CHAPTER IFood and Drug Administration, Department of Health and Human Services (Continued) ........................... 170


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CHAPTER IFOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH

AND HUMAN SERVICES (CONTINUED) (Parts 170 to 199)

EDITORIAL NOTE: Nomenclature changes to chapter I appear at 59 FR 14366, Mar. 28, 1994, and 69 FR 18803, Apr. 9, 2004.

SUBCHAPTER BFOOD FOR HUMAN CONSUMPTION (CONTINUED)

Part Page 170 Food additives ......................................................... 5 171 Food additive petitions ........................................... 24 172 Food additives permitted for direct addition to

food for human consumption ................................ 30 173 Secondary direct food additives permitted in food

for human consumption ....................................... 122 174 Indirect food additives: General .............................. 155 175 Indirect food additives: Adhesives and components

of coatings ............................................................ 156 176 Indirect food additives: Paper and paperboard com-

ponents ................................................................. 199 177 Indirect food additives: Polymers ........................... 238 178 Indirect food additives: Adjuvants, production

aids, and sanitizers ............................................... 360 179 Irradiation in the production, processing and han-

dling of food ......................................................... 454 180 Food additives permitted in food or in contact

with food on an interim basis pending additional study .................................................................... 460

181 Prior-sanctioned food ingredients ........................... 466 182 Substances generally recognized as safe ................. 470 184 Direct food substances affirmed as generally recog-

nized as safe ......................................................... 483 186 Indirect food substances affirmed as generally rec-

ognized as safe ...................................................... 588 189 Substances prohibited from use in human food ...... 594 190 Dietary supplements ............................................... 601 191199 [Reserved]


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SUBCHAPTER BFOOD FOR HUMAN CONSUMPTION (CONTINUED)

PART 170FOOD ADDITIVES

Subpart AGeneral Provisions

Sec. 170.3 Definitions. 170.6 Opinion letters on food additive sta-

tus. 170.10 Food additives in standardized foods. 170.15 Adoption of regulation on initiative

of Commissioner. 170.17 Exemption for investigational use

and procedure for obtaining authoriza-tion to market edible products from ex-perimental animals.

170.18 Tolerances for related food additives. 170.19 Pesticide chemicals in processed

foods.

Subpart BFood Additive Safety

170.20 General principles for evaluating the safety of food additives.

170.22 Safety factors to be considered. 170.30 Eligibility for classification as gen-

erally recognized as safe (GRAS). 170.35 Affirmation of generally recognized

as safe (GRAS) status. 170.38 Determination of food additive sta-

tus. 170.39 Threshold of regulation for sub-

stances used in food-contact articles.

Subpart CSpecific Administrative Rulings and Decisions

170.45 Fluorine-containing compounds. 170.50 Glycine (aminoacetic acid) in food for

human consumption. 170.60 Nitrites and/or nitrates in curing pre-

mixes.

Subpart DPremarket Notifications

170.100 Submission of a premarket notifica-tion for a food contact substance (FCN) to the Food and Drug Administration (FDA).

170.101 Information in a premarket notifica-tion for a food contact substance (FCN).

170.102 Confidentiality of information in a premarket notification for a food contact substance (FCN).

170.103 Withdrawal without prejudice of a premarket notification for a food contact substance (FCN).

170.104 Action on a premarket notification for a food contact substance (FCN).

170.105 The Food and Drug Administrations (FDAs) determination that a premarket notification for a food contact substance (FCN) is no longer effective.

170.106 Notification for a food contact sub-stance formulation (NFCSF).

AUTHORITY: 21 U.S.C. 321, 341, 342, 346a, 348, 371.

SOURCE: 42 FR 14483, Mar. 15, 1977, unless otherwise noted.

EDITORIAL NOTE: Nomenclature changes to part 170 appear at 66 FR 56035, Nov. 6, 2001 and 69 FR 13717, Mar. 24, 2004.

Subpart AGeneral Provisions 170.3 Definitions.

For the purposes of this subchapter, the following definitions apply:

(a) Secretary means the Secretary of Health and Human Services.

(b) Department means the Department of Health and Human Services.

(c) Commissioner means the Commis-sioner of Food and Drugs.

(d) As used in this part, the term act means the Federal Food, Drug, and Cosmetic Act approved June 25, 1936, 52 Stat. 1040 et seq., as amended (21 U.S.C. 301392).

(e)(1) Food additives includes all sub-stances not exempted by section 201(s) of the act, the intended use of which results or may reasonably be expected to result, directly or indirectly, either in their becoming a component of food or otherwise affecting the characteris-tics of food. A material used in the pro-duction of containers and packages is subject to the definition if it may rea-sonably be expected to become a com-ponent, or to affect the characteristics, directly or indirectly, of food packed in the container. Affecting the charac-teristics of food does not include such physical effects, as protecting contents of packages, preserving shape, and pre-venting moisture loss. If there is no migration of a packaging component from the package to the food, it does not become a component of the food and thus is not a food additive. A sub-stance that does not become a compo-nent of food, but that is used, for exam-ple, in preparing an ingredient of the food to give a different flavor, texture, or other characteristic in the food, may be a food additive.


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21 CFR Ch. I (4113 Edition) 170.3

(2) Uses of food additives not requiring a listing regulation. Use of a substance in a food contact article (e.g., food- packaging or food-processing equip-ment) whereby the substance migrates, or may reasonably be expected to mi-grate, into food at such levels that the use has been exempted from regulation as a food additive under 170.39, and food contact substances used in accord-ance with a notification submitted under section 409(h) of the act that is effective.

(3) A food contact substance is any sub-stance that is intended for use as a component of materials used in manu-facturing, packing, packaging, trans-porting, or holding food if such use is not intended to have any technical ef-fect in such food.

(f) Common use in food means a sub-stantial history of consumption of a substance for food use by a significant number of consumers.

(g) The word substance in the defini-tion of the term food additive in-cludes a food or food component con-sisting of one or more ingredients.

(h) Scientific procedures include those human, animal, analytical, and other scientific studies, whether published or unpublished, appropriate to establish the safety of a substance.

(i) Safe or safety means that there is a reasonable certainty in the minds of competent scientists that the sub-stance is not harmful under the in-tended conditions of use. It is impos-sible in the present state of scientific knowledge to establish with complete certainty the absolute harmlessness of the use of any substance. Safety may be determined by scientific procedures or by general recognition of safety. In determining safety, the following fac-tors shall be considered:

(1) The probable consumption of the substance and of any substance formed in or on food because of its use.

(2) The cumulative effect of the sub-stance in the diet, taking into account any chemically or pharmacologically related substance or substances in such diet.

(3) Safety factors which, in the opin-ion of experts qualified by scientific training and experience to evaluate the safety of food and food ingredients, are generally recognized as appropriate.

(j) The term nonperishable processed food means any processed food not sub-ject to rapid decay or deterioration that would render it unfit for consump-tion. Examples are flour, sugar, cere-als, packaged cookies, and crackers. Not included are hermetically sealed foods or manufactured dairy products and other processed foods requiring re-frigeration.

(k) General recognition of safety shall be determined in accordance with 170.30.

(l) Prior sanction means an explicit approval granted with respect to use of a substance in food prior to September 6, 1958, by the Food and Drug Adminis-tration or the United States Depart-ment of Agriculture pursuant to the Federal Food, Drug, and Cosmetic Act, the Poultry Products Inspection Act, or the Meat Inspection Act.

(m) Food includes human food, sub-stances migrating to food from food- contact articles, pet food, and animal feed.

(n) The following general food cat-egories are established to group spe-cific related foods together for the pur-pose of establishing tolerances or limi-tations for the use of direct human food ingredients. Individual food prod-ucts will be included within these cat-egories according to the detailed clas-sifications lists contained in Exhibit 33B of the report of the National Acad-emy of Sciences/National Research Council report, A Comprehensive Sur-vey of Industry on the Use of Food Chemicals Generally Recognized as Safe (September 1972), which is incor-porated by reference. Copies are avail-able from the National Technical Infor-mation Service (NTIS), 5285 Port Royal Rd., Springfield, VA 22161, or at the Na-tional Archives and Records Adminis-tration (NARA). For information on the availability of this material at NARA, call 2027416030, or go to: http:// www.archives.gov/federallregister/ codeloflfederallregulations/ ibrllocations.html.

(1) Baked goods and baking mixes, in-cluding all ready-to-eat and ready-to- bake products, flours, and mixes re-quiring preparation before serving.

(2) Beverages, alcoholic, including malt beverages, wines, distilled liq-uors, and cocktail mix.


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Food and Drug Administration, HHS 170.3

(3) Beverages and beverage bases, nonalcoholic, including only special or spiced teas, soft drinks, coffee sub-stitutes, and fruit and vegetable fla-vored gelatin drinks.

(4) Breakfast cereals, including ready-to-eat and instant and regular hot cereals.

(5) Cheeses, including curd and whey cheeses, cream, natural, grating, proc-essed, spread, dip, and miscellaneous cheeses.

(6) Chewing gum, including all forms. (7) Coffee and tea, including regular,

decaffeinated, and instant types. (8) Condiments and relishes, includ-

ing plain seasoning sauces and spreads, olives, pickles, and relishes, but not spices or herbs.

(9) Confections and frostings, includ-ing candy and flavored frostings, marshmallows, baking chocolate, and brown, lump, rock, maple, powdered, and raw sugars.

(10) Dairy product analogs, including nondairy milk, frozen or liquid cream-ers, coffee whiteners, toppings, and other nondairy products.

(11) Egg products, including liquid, frozen, or dried eggs, and egg dishes made therefrom, i.e., egg roll, egg foo young, egg salad, and frozen multi-course egg meals, but not fresh eggs.

(12) Fats and oils, including mar-garine, dressings for salads, butter, salad oils, shortenings and cooking oils.

(13) Fish products, including all pre-pared main dishes, salads, appetizers, frozen multicourse meals, and spreads containing fish, shellfish, and other aquatic animals, but not fresh fish.

(14) Fresh eggs, including cooked eggs and egg dishes made only from fresh shell eggs.

(15) Fresh fish, including only fresh and frozen fish, shellfish, and other aquatic animals.

(16) Fresh fruits and fruit juices, in-cluding only raw fruits, citrus, melons, and berries, and home-prepared ades and punches made therefrom.

(17) Fresh meats, including only fresh or home-frozen beef or veal, pork, lamb or mutton and home-prepared fresh meat-containing dishes, salads, appe-tizers, or sandwich spreads made there-from.

(18) Fresh poultry, including only fresh or home-frozen poultry and game birds and home-prepared fresh poultry- containing dishes, salads, appetizers, or sandwich spreads made therefrom.

(19) Fresh vegetables, tomatoes, and potatoes, including only fresh and home-prepared vegetables.

(20) Frozen dairy desserts and mixes, including ice cream, ice milks, sher-bets, and other frozen dairy desserts and specialties.

(21) Fruit and water ices, including all frozen fruit and water ices.

(22) Gelatins, puddings, and fillings, including flavored gelatin desserts, puddings, custards, parfaits, pie fill-ings, and gelatin base salads.

(23) Grain products and pastas, in-cluding macaroni and noodle products, rice dishes, and frozen multicourse meals, without meat or vegetables.

(24) Gravies and sauces, including all meat sauces and gravies, and tomato, milk, buttery, and specialty sauces.

(25) Hard candy and cough drops, in-cluding all hard type candies.

(26) Herbs, seeds, spices, seasonings, blends, extracts, and flavorings, includ-ing all natural and artificial spices, blends, and flavors.

(27) Jams and jellies, home-prepared, including only home-prepared jams, jellies, fruit butters, preserves, and sweet spreads.

(28) Jams and jellies, commercial, in-cluding only commercially processed jams, jellies, fruit butters, preserves, and sweet spreads.

(29) Meat products, including all meats and meat containing dishes, sal-ads, appetizers, frozen multicourse meat meals, and sandwich ingredients prepared by commercial processing or using commercially processed meats with home preparation.

(30) Milk, whole and skim, including only whole, lowfat, and skim fluid milks.

(31) Milk products, including flavored milks and milk drinks, dry milks, top-pings, snack dips, spreads, weight con-trol milk beverages, and other milk or-igin products.

(32) Nuts and nut products, including whole or shelled tree nuts, peanuts, co-conut, and nut and peanut spreads.


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21 CFR Ch. I (4113 Edition) 170.3

(33) Plant protein products, including the National Academy of Sciences/Na-tional Research Council reconstituted vegetable protein category, and meat, poultry, and fish substitutes, analogs, and extender products made from plant proteins.

(34) Poultry products, including all poultry and poultry-containing dishes, salads, appetizers, frozen multicourse poultry meals, and sandwich ingredi-ents prepared by commercial proc-essing or using commercially processed poultry with home preparation.

(35) Processed fruits and fruit juices, including all commercially processed fruits, citrus, berries, and mixtures; salads, juices and juice punches, con-centrates, dilutions, ades, and drink substitutes made therefrom.

(36) Processed vegetables and vege-table juices, including all commer-cially processed vegetables, vegetable dishes, frozen multicourse vegetable meals, and vegetable juices and blends.

(37) Snack foods, including chips, pretzels, and other novelty snacks.

(38) Soft candy, including candy bars, chocolates, fudge, mints, and other chewy or nougat candies.

(39) Soups, home-prepared, including meat, fish, poultry, vegetable, and combination home-prepared soups.

(40) Soups and soup mixes, including commercially prepared meat, fish, poultry, vegetable, and combination soups and soup mixes.

(41) Sugar, white, granulated, includ-ing only white granulated sugar.

(42) Sugar substitutes, including granulated, liquid, and tablet sugar substitutes.

(43) Sweet sauces, toppings, and syr-ups, including chocolate, berry, fruit, corn syrup, and maple sweet sauces and toppings.

(o) The following terms describe the physical or technical functional effects for which direct human food ingredi-ents may be added to foods. They are adopted from the National Academy of Sciences/National Research Council na-tional survey of food industries, re-ported to the Food and Drug Adminis-tration under the contract title A Comprehensive Survey of Industry on the Use of Food Chemicals Generally Recognized as Safe (September 1972), which is incorporated by reference.

Copies are available from the National Technical Information Service (NTIS), 5285 Port Royal Rd., Springfield, VA 22161, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 2027416030, or go to: http://www.archives.gov/ federallregister/ codeloflfederallregulations/ ibrllocations.html.

(1) Anticaking agents and free-flow agents: Substances added to finely pow-dered or crystalline food products to prevent caking, lumping, or agglomer-ation.

(2) Antimicrobial agents: Substances used to preserve food by preventing growth of microorganisms and subse-quent spoilage, including fungistats, mold and rope inhibitors, and the ef-fects listed by the National Academy of Sciences/National Research Council under preservatives.

(3) Antioxidants: Substances used to preserve food by retarding deteriora-tion, rancidity, or discoloration due to oxidation.

(4) Colors and coloring adjuncts: Sub-stances used to impart, preserve, or en-hance the color or shading of a food, in-cluding color stabilizers, color fixa-tives, color-retention agents, etc.

(5) Curing and pickling agents: Sub-stances imparting a unique flavor and/ or color to a food, usually producing an increase in shelf life stability.

(6) Dough strengtheners: Substances used to modify starch and gluten, thereby producing a more stable dough, including the applicable effects listed by the National Academy of Sciences/ National Research Council under dough conditioner.

(7) Drying agents: Substances with moisture-absorbing ability, used to maintain an environment of low mois-ture.

(8) Emulsifiers and emulsifier salts: Substances which modify surface ten-sion in the component phase of an emulsion to establish a uniform disper-sion or emulsion.

(9) Enzymes: Enzymes used to im-prove food processing and the quality of the finished food.

(10) Firming agents: Substances added to precipitate residual pectin, thus strengthening the supporting tissue


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and preventing its collapse during processing.

(11) Flavor enhancers: Substances added to supplement, enhance, or mod-ify the original taste and/or aroma of a food, without imparting a char-acteristic taste or aroma of its own.

(12) Flavoring agents and adjuvants: Substances added to impart or help im-part a taste or aroma in food.

(13) Flour treating agents: Substances added to milled flour, at the mill, to improve its color and/or baking quali-ties, including bleaching and maturing agents.

(14) Formulation aids: Substances used to promote or produce a desired phys-ical state or texture in food, including carriers, binders, fillers, plasticizers, film-formers, and tableting aids, etc.

(15) Fumigants: Volatile substances used for controlling insects or pests.

(16) Humectants: Hygroscopic sub-stances incorporated in food to pro-mote retention of moisture, including moisture-retention agents and anti-dusting agents.

(17) Leavening agents: Substances used to produce or stimulate produc-tion of carbon dioxide in baked goods to impart a light texture, including yeast, yeast foods, and calcium salts listed by the National Academy of Sciences/National Research Council under dough conditioners.

(18) Lubricants and release agents: Sub-stances added to food contact surfaces to prevent ingredients and finished products from sticking to them.

(19) Non-nutritive sweeteners: Sub-stances having less than 2 percent of the caloric value of sucrose per equiva-lent unit of sweetening capacity.

(20) Nutrient supplements: Substances which are necessary for the bodys nu-tritional and metabolic processes.

(21) Nutritive sweeteners: Substances having greater than 2 percent of the ca-loric value of sucrose per equivalent unit of sweetening capacity.

(22) Oxidizing and reducing agents: Substances which chemically oxidize or reduce another food ingredient, thereby producing a more stable prod-uct, including the applicable effect list-ed by the National Academy of Sciences/National Research Council under dough conditioners.

(23) pH control agents: Substances added to change or maintain active acidity or basicity, including buffers, acids, alkalies, and neutralizing agents.

(24) Processing aids: Substances used as manufacturing aids to enhance the appeal or utility of a food or food com-ponent, including clarifying agents, clouding agents, catalysts, flocculents, filter aids, and crystallization inhibi-tors, etc.

(25) Propellants, aerating agents, and gases: Gases used to supply force to expel a product or used to reduce the amount of oxygen in contact with the food in packaging.

(26) Sequestrants: Substances which combine with polyvalent metal ions to form a soluble metal complex, to im-prove the quality and stability of prod-ucts.

(27) Solvents and vehicles: Substances used to extract or dissolve another sub-stance.

(28) Stabilizers and thickeners: Sub-stances used to produce viscous solu-tions or dispersions, to impart body, improve consistency, or stabilize emul-sions, including suspending and body-ing agents, setting agents, jellying agents, and bulking agents, etc.

(29) Surface-active agents: Substances used to modify surface properties of liquid food components for a variety of effects, other than emulsifiers, but in-cluding solubilizing agents, dispersants, detergents, wetting agents, rehydration enhancers, whip-ping agents, foaming agents, and de-foaming agents, etc.

(30) Surface-finishing agents: Sub-stances used to increase palatability, preserve gloss, and inhibit discolora-tion of foods, including glazes, polishes, waxes, and protective coatings.

(31) Synergists: Substances used to act or react with another food ingredient to produce a total effect different or greater than the sum of the effects pro-duced by the individual ingredients.

(32) Texturizers: Substances which af-fect the appearance or feel of the food.

[42 FR 14483, Mar. 15, 1977, as amended at 47 FR 11835, Mar. 19, 1982; 53 FR 16546, May 10, 1988; 54 FR 24896, June 12, 1989; 60 FR 36595, July 17, 1995; 67 FR 35729, May 21, 2002]


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21 CFR Ch. I (4113 Edition) 170.6

170.6 Opinion letters on food addi-tive status.

(a) Over the years the Food and Drug Administration has given informal written opinions to inquiries as to the safety of articles intended for use as components of, or in contact with, food. Prior to the enactment of the Food Additives Amendment of 1958 (Pub. L. 85929; Sept. 6, 1958), these opinions were given pursuant to sec-tion 402(a)(1) of the Federal Food, Drug, and Cosmetic Act, which reads in part: A food shall be deemed to be adulterated if it bears or contains any poisonous or deleterious substance which may render it injurious to health.

(b) Since enactment of the Food Ad-ditives Amendment, the Food and Drug Administration has advised such in-quirers that an article:

(1) Is a food additive within the meaning of section 201(s) of the act; or

(2) Is generally recognized as safe (GRAS); or

(3) Has prior sanction or approval under that amendment; or

(4) Is not a food additive under the conditions of intended use.

(c) In the interest of the public health, such articles which have been considered in the past by the Food and Drug Administration to be safe under the provisions of section 402(a)(1), or to be generally recognized as safe for their intended use, or to have prior sanction or approval, or not to be food additives under the conditions of in-tended use, must be reexamined in the light of current scientific information and current principles for evaluating the safety of food additives if their use is to be continued.

(d) Because of the time span in-volved, copies of many of the letters in which the Food and Drug Administra-tion has expressed an informal opinion concerning the status of such articles may no longer be in the file of the Food and Drug Administration. In the ab-sence of information concerning the names and uses made of all the articles referred to in such letters, their safety of use cannot be reexamined. For this reason all food additive status opinions of the kind described in paragraph (c) of this section given by the Food and

Drug Administration are hereby re-voked.

(e) The prior opinions of the kind de-scribed in paragraph (c) of this section will be replaced by qualified and cur-rent opinions if the recipient of each such letter forwards a copy of each to the Department of Health and Human Services, Food and Drug Administra-tion, Center for Food Safety and Ap-plied Nutrition, 5100 Paint Branch Pkwy., College Park, MD 20740, along with a copy of his letter of inquiry, on or before July 23, 1970.

(f) This section does not apply to food additive status opinion letters per-taining to articles that were considered by the Food and Drug Administration to be food additives nor to articles in-cluded in regulations in parts 170 through 189 of this chapter if the arti-cles are used in accordance with the re-quirements of such regulations.

[42 FR 14483, Mar. 15, 1977, as amended at 54 FR 24896, June 12, 1989]

170.10 Food additives in standard-ized foods.

(a) The inclusion of food ingredients in parts 170 through 189 of this chapter does not imply that these ingredients may be used in standardized foods un-less they are recognized as optional in-gredients in applicable food standards. Where a petition is received for the issuance or amendment of a regulation establishing a definition and standard of identity for a food under section 401 of the Act, which proposes the inclu-sion of a food additive in such defini-tion and standard of identity, the pro-visions of the regulations in this part shall apply with respect to the infor-mation that must be submitted with respect to the food additive. Since sec-tion 409(b)(5) of the Act requires that the Secretary publish notice of a peti-tion for the establishment of a food-ad-ditive regulation within 30 days after filing, notice of a petition relating to a definition and standard of identity shall also be published within that time limitation if it includes a request, so designated, for the establishment of a regulation pertaining to a food addi-tive.

(b) If a petition for a definition and standard of identity contains a pro-posal for a food-additive regulation,


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and the petitioner fails to designate it as such, the Commissioner, upon deter-mining that the petition includes a proposal for a food-additive regulation, shall so notify the petitioner and shall thereafter proceed in accordance with the regulations in this part.

(c) A regulation will not be issued al-lowing the use of a food additive in a food for which a definition and stand-ard of identity is established, unless its issuance is in conformity with section 401 of the Act or with the terms of a temporary permit issued under 130.17 of this chapter. When the contemplated use of such additive complies with the terms of a temporary permit, the food additive regulation will be conditioned on such compliance and will expire with the expiration of the temporary permit.

170.15 Adoption of regulation on ini-tiative of Commissioner.

(a) The Commissioner upon his own initiative may propose the issuance of a regulation prescribing, with respect to any particular use of a food additive, the conditions under which such addi-tive may be safely used. Notice of such proposal shall be published in the FED-ERAL REGISTER and shall state the rea-sons for the proposal.

(b) Action upon a proposal made by the Commissioner shall proceed as pro-vided in part 10 of this chapter.

[42 FR 14486, Mar. 15, 1977, as amended at 42 FR 15673, Mar. 22, 1977]

170.17 Exemption for investigational use and procedure for obtaining au-thorization to market edible prod-ucts from experimental animals.

A food additive or food containing a food additive intended for investiga-tional use by qualified experts shall be exempt from the requirements of sec-tion 409 of the Act under the following conditions:

(a) If intended for investigational use in vitro or in laboratory research ani-mals, it bears a label which states prominently, in addition to the other information required by the act, the warning:

Caution. Contains a new food additive for investigational use only in laboratory re-search animals or for tests in vitro. Not for use in humans.

(b) If intended for use in animals other than laboratory research animals and if the edible products of the ani-mals are to be marketed as food, per-mission for the marketing of the edible products as food has been requested by the sponsor, and authorization has been granted by the Food and Drug Ad-ministration in accordance with 511.1 of this chapter or by the Department of Agriculture in accordance with 9 CFR 309.17, and it bears a label which states prominently, in addition to the other information required by the Act, the warning:

Caution. Contains a new food additive for use only in investigational animals. Not for use in humans.

Edible products of investigational animals are not to be used for food unless authoriza-tion has been granted by the U.S. Food and Drug Administration or by the U.S. Depart-ment of Agriculture.

(c) If intended for nonclinical labora-tory studies in food-producing animals, the study is conducted in compliance with the regulations set forth in part 58 of this chapter.

[42 FR 14483, Mar. 15, 1977, as amended at 43 FR 60021, Dec. 22, 1978]

170.18 Tolerances for related food ad-ditives.

(a) Food additives that cause similar or related pharmacological effects will be regarded as a class, and in the ab-sence of evidence to the contrary, as having additive toxic effects and will be considered as related food additives.

(b) Tolerances established for such related food additives may limit the amount of a common component that may be present, or may limit the amount of biological activity (such as cholinesterase inhibition) that may be present or may limit the total amount of related food additives that may be present.

(c) Where food additives from two or more chemicals in the same class are present in or on a food, the tolerance for the total of such additives shall be the same as that for the additive hav-ing the lowest numerical tolerance in this class, unless there are available methods that permit quantitative de-termination of the amount of each food additive present or unless it is shown that a higher tolerance is reasonably


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21 CFR Ch. I (4113 Edition) 170.19

required for the combined additives to accomplish the physical or technical effect for which such combined addi-tives are intended and that the higher tolerance will be safe.

(d) Where residues from two or more additives in the same class are present in or on a food and there are available methods that permit quantitative de-termination of each residue, the quan-tity of combined residues that are within the tolerance may be deter-mined as follows:

(1) Determine the quantity of each residue present.

(2) Divide the quantity of each res-idue by the tolerance that would apply if it occurred alone, and multiply by 100 to determine the percentage of the permitted amount of residue present.

(3) Add the percentages so obtained for all residues present.

(4) The sum of the percentage shall not exceed 100 percent.

170.19 Pesticide chemicals in proc-essed foods.

When pesticide chemical residues occur in processed foods due to the use of raw agricultural commodities that bore or contained a pesticide chemical in conformity with an exemption granted or a tolerance prescribed under section 408 of the Act, the processed food will not be regarded as adulter-ated so long as good manufacturing practice has been followed in removing any residue from the raw agricultural commodity in the processing (such as by peeling or washing) and so long as the concentration of the residue in the processed food when ready to eat is not greater than the tolerance prescribed for the raw agricultural commodity. But when the concentration of residue in the processed food when ready to eat is higher than the tolerance prescribed for the raw agricultural commodity, the processed food is adulterated unless the higher concentration is permitted by a tolerance obtained under section 409 of the Act. For example, if fruit bearing a residue of 7 parts per million of DDT permitted on the raw agricul-tural commodity is dried and a residue in excess of 7 parts per million of DDT results on the dried fruit, the dehy-drated fruit is adulterated unless the higher tolerance for DDT is authorized

by the regulations in this part. Food that is itself ready to eat, and which contains a higher residue than allowed for the raw agricultural commodity, may not be legalized by blending or mixing with other foods to reduce the residue in the mixed food below the tol-erance prescribed for the raw agricul-tural commodity.

Subpart BFood Additive Safety

170.20 General principles for evalu-ating the safety of food additives.

(a) In reaching a decision on any pe-tition filed under section 409 of the Act, the Commissioner will give full consideration to the specific biological properties of the compound and the adequacy of the methods employed to demonstrate safety for the proposed use, and the Commissioner will be guided by the principles and procedures for establishing the safety of food addi-tives stated in current publications of the National Academy of Sciences-Na-tional Research Council. A petition will not be denied, however, by reason of the petitioners having followed pro-cedures other than those outlined in the publications of the National Acad-emy of Sciences-National Research Council if, from available evidence, the Commissioner finds that the proce-dures used give results as reliable as, or more reliable than, those reasonably to be expected from the use of the out-lined procedures. In reaching a deci-sion, the Commissioner will give due weight to the anticipated levels and patterns of consumption of the additive specified or reasonably inferrable. For the purposes of this section, the prin-ciples for evaluating safety of additives set forth in the abovementioned publi-cations will apply to any substance that may properly be classified as a food additive as defined in section 201(s) of the Act.

(b) Upon written request describing the proposed use of an additive and the proposed experiments to determine its safety, the Commissioner will advise a person who wishes to establish the safety of a food additive whether he be-lieves the experiments planned will yield data adequate for an evaluation of the safety of the additive.


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170.22 Safety factors to be consid-ered.

In accordance with section 409(c)(5)(C) of the Act, the following safety factors will be applied in deter-mining whether the proposed use of a food additive will be safe: Except where evidence is submitted which justifies use of a different safety factor, a safety factor in applying animal experimen-tation data to man of 100 to 1, will be used; that is, a food additive for use by man will not be granted a tolerance that will exceed 1100th of the maximum amount demonstrated to be without harm to experimental animals.

170.30 Eligibility for classification as generally recognized as safe (GRAS).

(a) General recognition of safety may be based only on the views of experts qualified by scientific training and ex-perience to evaluate the safety of sub-stances directly or indirectly added to food. The basis of such views may be ei-ther (1) scientific procedures or (2) in the case of a substance used in food prior to January 1, 1958, through expe-rience based on common use in food. General recognition of safety requires common knowledge about the sub-stance throughout the scientific com-munity knowledgeable about the safety of substances directly or indirectly added to food.

(b) General recognition of safety based upon scientific procedures shall require the same quantity and quality of scientific evidence as is required to obtain approval of a food additive regu-lation for the ingredient. General rec-ognition of safety through scientific procedures shall ordinarily be based upon published studies which may be corroborated by unpublished studies and other data and information.

(c)(1) General recognition of safety through experience based on common use in food prior to January 1, 1958, may be determined without the quan-tity or quality of scientific procedures required for approval of a food additive regulation. General recognition of safe-ty through experience based on com-mon use in food prior to January 1, 1958, shall be based solely on food use of the substance prior to January 1, 1958, and shall ordinarily be based upon

generally available data and informa-tion. An ingredient not in common use in food prior to January 1, 1958, may achieve general recognition of safety only through scientific procedures.

(2) A substance used in food prior to January 1, 1958, may be generally rec-ognized as safe through experience based on its common use in food when that use occurred exclusively or pri-marily outside of the United States if the information about the experience establishes that the use of the sub-stance is safe within the meaning of the act (see 170.3(i)). Common use in food prior to January 1, 1958, that oc-curred outside of the United States shall be documented by published or other information and shall be corrobo-rated by information from a second, independent source that confirms the history and circumstances of use of the substance. The information used to document and to corroborate the his-tory and circumstances of use of the substance must be generally available; that is, it must be widely available in the country in which the history of use has occurred and readily available to interested qualified experts in this country. Persons claiming GRAS sta-tus for a substance based on its com-mon use in food outside of the United States should obtain FDA concurrence that the use of the substance is GRAS.

(d) The food ingredients listed as GRAS in part 182 of this chapter or af-firmed as GRAS in part 184 or 186.1 of this chapter do not include all sub-stances that are generally recognized as safe for their intended use in food. Because of the large number of sub-stances the intended use of which re-sults or may reasonably be expected to result, directly or indirectly, in their becoming a component or otherwise af-fecting the characteristics of food, it is impracticable to list all such sub-stances that are GRAS. A food ingre-dient of natural biological origin that has been widely consumed for its nutri-ent properties in the United States prior to January 1, 1958, without known detrimental effects, which is subject only to conventional processing as practiced prior to January 1, 1958, and for which no known safety hazard ex-ists, will ordinarily be regarded as GRAS without specific inclusion in


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21 CFR Ch. I (4113 Edition) 170.30

part 182, part 184 or 186.1 of this chap-ter.

(e) Food ingredients were listed as GRAS in part 182 of this chapter during 19581962 without a detailed scientific review of all available data and infor-mation relating to their safety. Begin-ning in 1969, the Food and Drug Admin-istration has undertaken a systematic review of the status of all ingredients used in food on the determination that they are GRAS or subject to a prior sanction. All determinations of GRAS status or food additive status or prior sanction status pursuant to this review shall be handled pursuant to 170.35, 170.38, and 180.1 of this chapter. Affir-mation of GRAS status shall be an-nounced in part 184 or 186.1 of this chapter.

(f) The status of the following food ingredients will be reviewed and af-firmed as GRAS or determined to be a food additive or subject to a prior sanc-tion pursuant to 170.35, 170.38, or 180.1 of this chapter:

(1) Any substance of natural biologi-cal origin that has been widely con-sumed for its nutrient properties in the United States prior to January 1, 1958, without known detrimental effect, for which no health hazard is known, and which has been modified by processes first introduced into commercial use after January 1, 1958, which may rea-sonably be expected significantly to alter the composition of the substance.

(2) Any substance of natural biologi-cal origin that has been widely con-sumed for its nutrient properties in the United States prior to January 1, 1958, without known detrimental effect, for which no health hazard is known, that has had significant alteration of com-position by breeding or selection after January 1, 1958, where the change may be reasonably expected to alter the nu-tritive value or the concentration of toxic constituents.

(3) Distillates, isolates, extracts, and concentration of extracts of GRAS sub-stances.

(4) Reaction products of GRAS sub-stances.

(5) Substances not of a natural bio-logical origin, including those for which evidence is offered that they are identical to a GRAS counterpart of natural biological origin.

(6) Substances of natural biological origin intended for consumption for other than their nutrient properties.

(g) A food ingredient that is not GRAS or subject to a prior sanction re-quires a food additive regulation pro-mulgated under section 409 of the act before it may be directly or indirectly added to food.

(h) A food ingredient that is listed as GRAS in part 182 of this chapter or af-firmed as GRAS in part 184 or 186.1 of this chapter shall be regarded as GRAS only if, in addition to all the require-ments in the applicable regulation, it also meets all of the following require-ments:

(1) It complies with any applicable food grade specifications of the Food Chemicals Codex, 2d Ed. (1972), or, if specifically indicated in the GRAS af-firmation regulation, the Food Chemi-cals Codex, 3d Ed. (1981), which are in-corporated by reference, except that any substance used as a component of articles that contact food and affirmed as GRAS in 186.1 of this chapter shall comply with the specifications therein, or in the absence of such specifications, shall be of a purity suitable for its in-tended use. Copies may be obtained from the National Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202741 6030, or go to: http://www.archives.gov/ federallregister/ codeloflfederallregulations/ ibrllocations.html.

(2) It performs an appropriate func-tion in the food or food-contact article in which it is used.

(3) It is used at a level no higher than necessary to achieve its intended pur-pose in that food or, if used as a compo-nent of a food-contact article, at a level no higher than necessary to achieve its intended purpose in that ar-ticle.

(i) If a substance is affirmed as GRAS in part 184 or 186.1 of this chapter with no limitation other than good manu-facturing practice, it shall be regarded as GRAS if its conditions of use are not significantly different from those re-ported in the regulation as the basis on


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which the GRAS status of the sub-stance was affirmed. If the conditions of use are significantly different, such use of the substance may not be GRAS. In such a case a manufacturer may not rely on the regulation as authorizing the use but must independently estab-lish that the use is GRAS or must use the substance in accordance with a food additive regulation.

(j) If an ingredient is affirmed as GRAS in part 184 or 186.1 of this chap-ter with specific limitation(s), it may be used in food only within such limi-tation(s) (including the category of food(s), the functional use(s) of the in-gredient, and the level(s) of use). Any use of such an ingredient not in full compliance with each such established limitation shall require a food additive regulation.

(k) Pursuant to 170.35, a food ingre-dient may be affirmed as GRAS in part 184 or 186.1 of this chapter for a spe-cific use(s) without a general evalua-tion of use of the ingredient. In addi-tion to the use(s) specified in the regu-lation, other uses of such an ingredient may also be GRAS. Any affirmation of GRAS status for a specific use(s), with-out a general evaluation of use of the ingredient, is subject to reconsider-ation upon such evaluation.

(l) New information may at any time require reconsideration of the GRAS status of a food ingredient. Any change in part 182, part 184, or 186.1 of this chapter shall be accomplished pursuant to 170.38.

[42 FR 14483, Mar. 15, 1977, as amended at 49 FR 5610, Feb. 14, 1984; 53 FR 16546, May 10, 1988]

170.35 Affirmation of generally recog-nized as safe (GRAS) status.

(a) The Commissioner, either on his initiative or on the petition of an in-terested person, may affirm the GRAS status of substances that directly or indirectly become components of food.

(b)(1) If the Commissioner proposes on his own initiative that a substance is entitled to affirmation as GRAS, he will place all of the data and informa-tion on which he relies on public file in the office of the Division of Dockets Management and will publish in the FEDERAL REGISTER a notice giving the name of the substance, its proposed

uses, and any limitations proposed for purposes other than safety.

(2) The FEDERAL REGISTER notice will allow a period of 60 days during which any interested person may review the data and information and/or file com-ments with the Division of Dockets Management. Copies of all comments received shall be made available for ex-amination in the Division of Dockets Managements office.

(3) The Commissioner will evaluate all comments received. If he concludes that there is convincing evidence that the substance is GRAS as described in 170.30, he will publish a notice in the FEDERAL REGISTER listing the sub-stance as GRAS in part 182, part 184, or part 186 of this chapter, as appropriate.

(4) If, after evaluation of the com-ments, the Commissioner concludes that there is a lack of convincing evi-dence that the substance is GRAS and that it should be considered a food ad-ditive subject to section 409 of the Act, he shall publish a notice thereof in the FEDERAL REGISTER in accordance with 170.38.

(c)(1) Persons seeking the affirmation of GRAS status of substances as pro-vided in 170.30(e), except those subject to the NAS/NRC GRAS list survey (36 FR 20546; October 23, 1971), shall submit a petition for GRAS affirmation pursu-ant to part 10 of this chapter. Such pe-tition shall contain information to es-tablish that the GRAS criteria as set forth in 170.30 (b) or (c) have been met, in the following form:

(i) Description of the substance, in-cluding:

(a) Common or usual name. (b) Chemical name. (c) Chemical Abstract Service (CAS)

registry number. (d) Empirical formula. (e) Structural formula. (f) Specifications for food grade ma-

terial, including arsenic and heavy metals. (Recommendation for any change in the Food Chemicals Codex monograph should be included where applicable.)

(g) Quantitative compositions. (h) Manufacturing process (excluding

any trade secrets). (ii) Use of the substance, including: (a) Date when use began.


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21 CFR Ch. I (4113 Edition) 170.35

(b) Information and reports or other data on past uses in food.

(c) Foods in which used, and levels of use in such foods, and for what pur-poses.

(iii) Methods for detecting the sub-stance in food, including:

(a) References to qualitative and quantitative methods for determining the substance(s) in food, including the type of analytical procedures used.

(b) Sensitivity and reproducibility of such method(s).

(iv) Information to establish the safe-ty and functionality of the substance in food. Published scientific literature, evidence that the substance is identical to a GRAS counterpart of natural bio-logical origin, and other data may be submitted to support safety. Any ad-verse information or consumer com-plaints shall be included. Complete bib-liographic references shall be provided where a copy of the article is not pro-vided.

(v) A statement signed by the person responsible for the petition that to the best of his knowledge it is a represent-ative and balanced submission that in-cludes unfavorable information, as well as favorable information, known to him pertinent to the evaluation of the safety and functionality of the sub-stance.

(vi) If nonclinical laboratory studies are involved, additional information and data submitted in support of filed petitions shall include, with respect to each nonclinical study, either a state-ment that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compli-ance with such regulations, a brief statement of the reason for the non-compliance.

(vii) [Reserved] (viii) A claim for categorical exclu-

sion under 25.30 or 25.32 of this chap-ter or an environmental assessment under 25.40 of this chapter.

(2) Within 30 days after the date of filing the petition, the Commissioner will place the petition on public file in the office of the Division of Dockets Management and will publish a notice of filing in the FEDERAL REGISTER giv-ing the name of the petitioner and a brief description of the petition includ-

ing the name of the substance, its pro-posed use, and any limitations pro-posed for reasons other than safety. A copy of the notice will be mailed to the petitioner at the time the original is sent to the FEDERAL REGISTER.

(3)(i) If intended uses of the sub-stance include uses in meat, meat food product, or poultry product subject to regulation by the U.S. Department of Agriculture (USDA) under the Poultry Products Inspection Act (PPIA) (21 U.S.C. 451 et seq.) or Federal Meat In-spection Act (FMIA) (21 U.S.C. 601 et seq.), FDA shall, upon filing of the peti-tion, forward a copy of the petition or relevant portions thereof to the Food Safety and Inspection Service, USDA, for simultaneous review under the PPIA and FMIA.

(ii) FDA will ask USDA to advise whether the proposed meat and poultry uses comply with the FMIA and PPIA or, if not, whether use of the substance would be permitted in products under USDA jurisdiction under specified con-ditions or restrictions.

(4) The notice of filing in the FED-ERAL REGISTER will allow a period of 60 days during which any interested per-son may review the petition and/or file comments with the Division of Dockets Management. Copies of all comments received shall be made available for ex-amination in the Division of Dockets Managements office.

(5) The Commissioner will evaluate the petition and all available informa-tion including all comments received. If the petition and such information provide convincing evidence that the substance is GRAS as described in 170.30 he will publish an order in the FEDERAL REGISTER listing the sub-stance as GRAS in part 182, part 184, or part 186 of this chapter, as appropriate.

(6) If, after evaluation of the petition and all available information, the Com-missioner concludes that there is a lack of convincing evidence that the substance is GRAS and that it should be considered a food additive subject to section 409 of the Act, he shall publish a notice thereof in the FEDERAL REG-ISTER in accordance with 170.38.

(7) The notice of filing in the FED-ERAL REGISTER will request submission of proof of any applicable prior sanc-tion for use of the ingredient under


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conditions different from those pro-posed to be determined to be GRAS. The failure of any person to come for-ward with proof of such an applicable prior sanction in response to the notice of filing will constitute a waiver of the right to assert or rely on such sanction at any later time. The notice of filing will also constitute a proposal to estab-lish a regulation under part 181 of this chapter, incorporating the same provi-sions, in the event that such a regula-tion is determined to be appropriate as a result of submission of proof of such an applicable prior sanction in re-sponse to the notice of filing.

(Information collection requirements were approved by the Office of Management and Budget under control number 09100132)

[42 FR 14488, Mar. 15, 1977, as amended at 50 FR 7492, Feb. 22, 1985; 50 FR 16668, Apr. 26, 1985; 53 FR 16547, May 10, 1988; 62 FR 40599, July 29, 1997; 65 FR 51762, Aug. 25, 2000]

170.38 Determination of food addi-tive status.

(a) The Commissioner may, in ac-cordance with 170.35(b)(4) or (c)(5), publish a notice in the FEDERAL REG-ISTER determining that a substance is not GRAS and is a food additive sub-ject to section 409 of the Act.

(b)(1) The Commissioner, on his own initiative or on the petition of any in-terested person, pursuant to part 10 of this chapter, may issue a notice in the FEDERAL REGISTER proposing to deter-mine that a substance is not GRAS and is a food additive subject to section 409 of the Act. Any petition shall include all relevant data and information of the type described in 171.130(b). The Commissioner will place all of the data and information on which he relies on public file in the office of the Division of Dockets Management and will in-clude in the FEDERAL REGISTER notice the name of the substance, its known uses, and a summary of the basis for the determination.

(2) The FEDERAL REGISTER notice will allow a period of 60 days during which any interested person may review the data and information and/or file com-ments with the Division of Dockets Management. Copies of all comments shall be made available for examina-tion in the Division of Dockets Man-agements office.

(3) The Commissioner will evaluate all comments received. If he concludes that there is a lack of convincing evi-dence that the substance is GRAS or is otherwise exempt from the definition of a food additive in section 201(s) of the Act, he will publish a notice there-of in the FEDERAL REGISTER. If he con-cludes that there is convincing evi-dence that the substance is GRAS, he will publish an order in the FEDERAL REGISTER listing the substance as GRAS in part 182, part 184, or part 186 of this chapter, as appropriate.

(c) A FEDERAL REGISTER notice deter-mining that a substance is a food addi-tive shall provide for the use of the ad-ditive in food or food contact surfaces as follows:

(1) It may promulgate a food additive regulation governing use of the addi-tive.

(2) It may promulgate an interim food additive regulation governing use of the additive.

(3) It may require discontinuation of the use of the additive.

(4) It may adopt any combination of the above three approaches for dif-ferent uses or levels of use of the addi-tive.

(d) If the Commissioner of Food and Drugs is aware of any prior sanction for use of the substance, he will con-currently propose a separate regulation covering such use of the ingredient under part 181 of this chapter. If the Commissioner is unaware of any such applicable prior sanction, the proposed regulation will so state and will re-quire any person who intends to assert or rely on such sanction to submit proof of its existence. Any regulation promulgated pursuant to this section constitutes a determination that ex-cluded uses would result in adultera-tion of the food in violation of section 402 of the Act, and the failure of any person to come forward with proof of such an applicable prior sanction in re-sponse to the proposal will constitute a waiver of the right to assert or rely on such sanction at any later time. The notice will also constitute a proposal to establish a regulation under part 181 of this chapter, incorporating the same provisions, in the event that such a regulation is determined to be appro-priate as a result of submission of proof


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21 CFR Ch. I (4113 Edition) 170.39

of such an applicable prior sanction in response to the proposal.

[42 FR 14488, Mar. 15, 1977, as amended at 42 FR 15673, Mar. 22, 1977; 54 FR 24896, June 12, 1989]

170.39 Threshold of regulation for substances used in food-contact ar-ticles.

(a) A substance used in a food-con-tact article (e.g., food-packaging or food-processing equipment) that mi-grates, or that may be expected to mi-grate, into food will be exempted from regulation as a food additive because it becomes a component of food at levels that are below the threshold of regula-tion if:

(1) The substance has not been shown to be a carcinogen in humans or ani-mals, and there is no reason, based on the chemical structure of the sub-stance, to suspect that the substance is a carcinogen. The substance must also not contain a carcinogenic impurity or, if it does, must not contain a carcino-genic impurity with a TD50 value based on chronic feeding studies reported in the scientific literature or otherwise available to the Food and Drug Admin-istration of less than 6.25 milligrams per kilogram bodyweight per day (The TD50, for the purposes of this section, is the feeding dose that causes cancer in 50 percent of the test animals when corrected for tumors found in control animals. If more than one TD50 value has been reported in the scientific lit-erature for a substance, the Food and Drug Administration will use the low-est appropriate TD50 value in its re-view.);

(2) The substance presents no other health or safety concerns because:

(i) The use in question has been shown to result in or may be expected to result in dietary concentrations at or below 0.5 parts per billion, cor-responding to dietary exposure levels at or below 1.5 micrograms/person/day (based on a diet of 1,500 grams of solid food and 1,500 grams of liquid food per person per day); or

(ii) The substance is currently regu-lated for direct addition into food, and the dietary exposure to the substance resulting from the proposed use is at or below 1 percent of the acceptable daily intake as determined by safety data in

the Food and Drug Administrations files or from other appropriate sources;

(3) The substance has no technical ef-fect in or on the food to which it mi-grates; and

(4) The substance use has no signifi-cant adverse impact on the environ-ment.

(b) Notwithstanding paragraph (a) of this section, the Food and Drug Admin-istration reserves the right to decline to grant an exemption in those cases in which available information estab-lishes that the proposed use may pose a public health risk. The reasons for the agencys decision to decline to grant an exemption will be explained in the Food and Drug Administrations re-sponse to the requestor.

(c) A request for the Food and Drug Administration to exempt a use of a substance from regulation as a food ad-ditive shall include three copies of the following information (If part of the submitted material is in a foreign lan-guage, it must be accompanied by an English translation verified to be com-plete and accurate in accordance with 10.20(c)(2) of this chapter):

(1) The chemical composition of the substance for which the request is made, including, whenever possible, the name of the chemical in accord-ance with current Chemical Abstract Service (CAS) nomenclature guidelines and a CAS registry number, if avail-able;

(2) Detailed information on the con-ditions of use of the substance (e.g., temperature, type of food with which the substance will come into contact, the duration of the contact, and wheth-er the food-contact article will be for repeated or single use applications);

(3) A clear statement as to whether the request for exemption from regula-tion as a food additive is based on the fact that the use of the substance in the food-contact article results in a di-etary concentration at or below 0.5 parts per billion, or on the fact that it involves the use of a regulated direct food additive for which the dietary ex-posure is at or below 1 percent of the acceptable dietary intake (ADI);

(4) Data that will enable the Food and Drug Administration to estimate


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the daily dietary concentration result-ing from the proposed use of the sub-stance. These data should be in the form of:

(i) Validated migration data obtained under worst-case (time/temperature) intended use conditions utilizing ap-propriate food simulating solvents;

(ii) Information on the amount of the substance used in the manufacture of the food-contact article; or

(iii) Information on the residual level of the substance in the food-contact ar-ticle. For repeat-use articles, an esti-mate of the amount of food that con-tacts a specific unit of surface area over the lifetime of the article should also be provided. (In cases where data are provided only in the form of manu-facturing use levels or residual levels of the substance present in the food- contact article, the Food and Drug Ad-ministration will calculate a worst- case dietary concentration level as-suming 100 percent migration.) A de-tailed description of the analytical method used to quantify the substance should also be submitted along with data used to validate the detection limit.

(iv) In cases where there is no detect-able migration into food or food simulants, or when no residual level of a substance is detected in the food-con-tact article by a suitable analytical method, the Food and Drug Adminis-tration will, for the purposes of esti-mating the dietary concentration, con-sider the validated detection limit of the method used to analyze for the sub-stance.

(5) The results of an analysis of exist-ing toxicological information on the substance and its impurities. This in-formation on the substance is needed to show whether an animal carcinogen bioassay has been carried out, or whether there is some other basis for suspecting that the substance is a car-cinogen or potent toxin. This type of information on the impurities is need-ed to show whether any of them are carcinogenic, and, if carcinogenic, whether their TD50 values are greater than 6.25 milligrams per kilogram bodyweight per day in accordance with paragraph (a)(1) of this section.

(6) Information on the environmental impact that would result from the pro-

posed use of the substance. The request should contain either a claim for cat-egorical exclusion as specified in 25.32 of this chapter or an environmental as-sessment as specified in 25.40 of this chapter.

(d) Data to be reviewed under this section shall be submitted to the Food and Drug Administrations Office of Premarket Approval (HFS200), 5100 Paint Branch Pkwy., College Park, MD 20740.

(e) The Food and Drug Administra-tion will inform the requestor by letter whether the specific food-contact ap-plication is exempt from regulation as a food additive or not. Although a sub-stance that migrates to food at a level that results in a dietary concentration at or below the threshold of regulation will not be the subject of a regulation published in the FEDERAL REGISTER and will not appear in the Code of Fed-eral Regulations, the Food and Drug Administration will maintain a list of substances exempted from regulation as food additives under this section on display at the Division of Dockets Management. This list will include the name of the company that made the re-quest, the chemical name of the sub-stance, the specific use for which it has received an exemption from regulation as a food additive, and any appropriate limitations on its use. The list will not include any trade names. This list will enable interested persons to see the types of uses of food-contact materials being exempted under the regulation. Interested persons may also obtain a copy of the list of exempted substances by contacting the Food and Drug Ad-ministrations Office of Premarket Ap-proval (HFS200), 5100 Paint Branch Pkwy., College Park, MD 20740. For ac-tions requiring an environmental as-sessment, the agencys finding of no significant impact and the evidence supporting that finding, contained in the petitioners environmental assess-ment, also will be available for public inspection at the Division of Dockets Management in accordance with 25.51(b)(2) of this chapter. Requests for copies of releasable information con-tained in submissions requesting ex-emptions from the food additive regu-lations will be handled in accordance


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21 CFR Ch. I (4113 Edition) 170.45

with the Food and Drug Administra-tions Freedom of Information Act pro-cedures, as described in part 20 of this chapter. In particular, data and infor-mation that fall within the definitions of a trade secret or confidential com-mercial or financial information are not available for public disclosure in accordance with 20.61(c) of this chap-ter.

(f) If the request for an exemption from regulation as a food additive is not granted, the requestor may submit a petition to the Food and Drug Ad-ministration for reconsideration of the decision in accordance with the provi-sions of 10.33 of this chapter.

(g) If the Food and Drug Administra-tion receives significant new informa-tion that raises questions about the di-etary concentration or the safety of a substance that the agency has exempt-ed from regulation, the Food and Drug Administration may reevaluate the substance. If the Food and Drug Ad-ministration tentatively concludes that the information that is available about the substance no longer supports an exemption for the use of the food- contact material from the food addi-tive regulations, the agency will notify any persons that requested an exemp-tion for the substance of its tentative decision. The requestors will be given an opportunity to show why the use of the substance should not be regulated under the food additive provisions of the act. If the requestors fail to ade-quately respond to the new evidence, the agency will notify them that fur-ther use of the substance in question for the particular use will require a food additive regulation. This notifica-tion will be placed on public display at the Division of Dockets Management as part of the file of uses of substances exempted from regulation as food addi-tives. The Food and Drug Administra-tion recognizes that manufacturers other than those that actually made a request for exemption may also be using exempted substances in food-con-tact articles under conditions of use (e.g., use levels, temperature, type of food contacted, etc.) that are similar to those for which the exemption was issued. Because only requestors will be notified as part of the revocation proc-ess described in this section, the Food

and Drug Administration plans to no-tify other manufacturers by means of a notice published in the FEDERAL REG-ISTER of its decision to revoke an ex-emption issued for a specific use of a substance in a food contact article.

(h) Guidance documents to assist re-questors in the preparation of submis-sions seeking exemptions from the food additive regulations are available from the Food and Drug Administrations Office of Premarket Approval (HFS 200), 5100 Paint Branch Pkwy., College Park, MD 20740. Interested persons are encouraged to obtain specific guidance from the Food and Drug Administra-tion on the appropriate protocols to be used for obtaining migration data, on the validation of the analytical meth-ods used to quantify migration levels, on the procedures used to relate migra-tion data to dietary exposures, and on any other issue not specifically covered in the Food and Drug Administrations guidance documents.

[60 FR 36595, July 17, 1995, as amended at 62 FR 40599, July 29, 1997; 65 FR 56479, Sept. 19, 2000]

Subpart CSpecific Administra-tive Rulings and Decisions

170.45 Fluorine-containing com-pounds.

The Commissioner of Food and Drugs has c